Aspirin Has Some Benefits After Repeat VTE

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Aspirin failed to significantly reduce the recurrence of venous thromboembolism in patients who completed initial anticoagulant therapy, but it did lower the rate of major vascular events.

Note that aspirin reduced the secondary composite outcome of major vascular events such as myocardial infarction, stroke, or cardiovascular death without increasing bleeding and resulted in a significant net clinical benefit.

Aspirin failed to significantly reduce the recurrence of venous thromboembolism in patients who completed initial anticoagulant therapy, but it did lower the rate of major vascular events, researchers found.

Among adult patients who had completed warfarin therapy for a first episode of unprovoked venous thromboembolism (VTE), low-dose aspirin did not outperform placebo in reducing recurrent VTE (HR 0.74, 95% CI 0.52 to 1.05, P=0.09), according to Timothy Brighton, MB, of Prince of Wales Hospital in Sydney, Australia, and colleagues.

However, aspirin therapy significantly reduced rates of composites of VTE, myocardial infarction, stroke or cardiovascular death (HR 0.66, 95% CI 0.48 to 0.92, P=0.01) and of VTE, MI, stroke, major bleeding, or death by any cause (HR 0.67, 95% CI 0.49 to 0.91, P=0.01), they wrote in the New England Journal of Medicine.

The results showed that "aspirin reduced the secondary composite outcome of major vascular events by 34% without increasing bleeding and resulted in a significant net clinical benefit," they concluded, adding that aspirin was "substantially less effecting than warfarin," but "provides an attractive alternative" because of its cost, simplicity, and adverse event profile.

In an accompanying editorial, Theodore Warkentin, MD, said the current study results supported low-dose aspirin as a treatment option. He pointed out that the results bolster outcomes from an earlier study, The Warfarin and Aspirin (WARFASA).

WARFASA "showed a 42% reduction in the rate of recurrence of venous thromboembolism with aspirin as compared with placebo (HR 0.58, 95% CI 0.36 to 0.93, P=0.02)", wrote Warkentin, of McMaster University in Hamilton, Ontario.

"Among patients with unprovoked venous thromboembolism who have completed initial anticoagulation, aspirin would seem to be a reasonable option for long-term dual prevention," he added.

The researchers examined the use of low doses of aspirin because they are a "simple, inexpensive, and widely available" prospective alternative treatment options to vitamin K antagonists. They noted that vitamin K antagonist therapy has not been shown "to improve survival, is associated with a substantially increase risk of bleeding, and is inconvenient for patients."

Results from the current Aspirin to Prevent Recurrent Venous Thromboembolism (ASPIRE) study were also reported at the American Heart Association meeting in Los Angeles.

ASPIRE included 822 adult patients (mean age 54) who had completed initial anticoagulant therapy with warfarin after a first episode of unprovoked VTE. More than half were men (54%), 36% were obese, and 5% had had a previous provoked thromboembolism.

The study was conducted between 2003 and 2011 at 56 sites in five countries.

Patients were randomly assigned to 100 mg of aspirin daily or placebo for a minimum of 2 years and a maximum of 4 years. They were observed for recurrence of VTE with periodic follow-ups.

Patients took their assigned treatment for a median 27.2 months and the median follow-up was 37.2 months.

Secondary outcomes included major vascular events and measures of clinical net benefit, including reductions in the rate of the composite of VTE, MI, stroke, major bleeding, or death from any cause. The researchers also measured bleeding as a safety outcome.

Recurrent VTE occurred in 14% of patients receiving aspirin versus 18% of patients assigned to placebo at a rate of 4.8% versus 6.5% per year, a difference that failed to reach statistical significance.

Most of the recurrent DVT events (70%) without a concurrent PE occurred in patients who had been enrolled with a diagnosis of first unprovoked DVT alone, the authors reported.

Also, 73% of the recurrent PE events, with or without concurrent DVT, occurred in patients who were enrolled with a diagnosis of unprovoked PE with or without concurrent VTE.

There was no significant between-group difference in the rates of major or clinically relevant nonmajor bleeding episodes. The rate was 1.1% per year with aspirin and 0.6% per year with placebo (P=0.22). There also were no serious adverse events.

The study has some limitations. There was a relatively high rate of discontinuation of the study drug in ASPIRE so potential benefit of aspirin therapy is likely to have been underestimated.

Also, with a smaller patient population than originally planned for, the ASPIRE trial alone was not powered to show a significant reduction in the primary outcome, the authors explained.

However, pairing ASPIRE results with WARFASA results demonstrated a benefit. "The combined results of the WARFASA and ASPIRE trials show a highly significant reduction of 32% in the rate of recurrence of venous thromboembolism (P=0.007) and a reduction of 34% in the rate of major vascular events (P=0.002), with no excess of bleeding," they said.

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